Mechanistic insight into the induction of cellular immune responses by encapsulated and admixed archaeosome-based vaccine formulations
Archaeosomes are liposomes formulated using total polar lipids (TPLs) or semi-synthetic glycolipids derived from archaea. Conventional archaeosomes with entrapped antigen exhibit robust adjuvant activity as demonstrated by increased antigen-specific humoral and cell-mediated responses and enhanced p...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-09-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2020.1788300 |
| _version_ | 1827809519719153664 |
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| author | Gerard Agbayani Yimei Jia Bassel Akache Vandana Chandan Umar Iqbal Felicity C. Stark Lise Deschatelets Edmond Lam Usha D. Hemraz Sophie Régnier Lakshmi Krishnan Michael J. McCluskie |
| author_facet | Gerard Agbayani Yimei Jia Bassel Akache Vandana Chandan Umar Iqbal Felicity C. Stark Lise Deschatelets Edmond Lam Usha D. Hemraz Sophie Régnier Lakshmi Krishnan Michael J. McCluskie |
| author_sort | Gerard Agbayani |
| collection | DOAJ |
| description | Archaeosomes are liposomes formulated using total polar lipids (TPLs) or semi-synthetic glycolipids derived from archaea. Conventional archaeosomes with entrapped antigen exhibit robust adjuvant activity as demonstrated by increased antigen-specific humoral and cell-mediated responses and enhanced protective immunity in various murine infection and cancer models. However, antigen entrapment efficiency can vary greatly resulting in antigen loss during formulation and variable antigen:lipid ratios. In order to circumvent this, we recently developed an admixed archaeosome formulation composed of a single semi-synthetic archaeal lipid (SLA, sulfated lactosylarchaeol) which can induce similarly robust adjuvant activity as an encapsulated formulation. Herein, we evaluate and compare the mechanisms involved in the induction of early innate and antigen-specific responses by both admixed (Adm) and encapsulated (Enc) SLA archaeosomes. We demonstrate that both archaeosome formulations result in increased immune cell infiltration, enhanced antigen retention at injection site and increased antigen uptake by antigen-presenting cells and other immune cell types, including neutrophils and monocytes following intramuscular injection to mice using ovalbumin as a model antigen. In vitro studies demonstrate SLA in either formulation is preferentially taken up by macrophages. Although the encapsulated formulation was better able to induce antigen-specific CD8+ T cell activation by dendritic cells in vitro, both encapsulated and admixed formulations gave equivalently enhanced protection from tumor challenge when tested in vivo using a B16-OVA melanoma model. Despite some differences in the immunostimulatory profile relative to the SLA (Enc) formulation, SLA (Adm) induces strong in vivo immunogenicity and efficacy, while offering an ease of formulation. |
| first_indexed | 2024-03-11T22:42:32Z |
| format | Article |
| id | doaj.art-3e7ef0b9480d48b5baae17d096234b45 |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:42:32Z |
| publishDate | 2020-09-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-3e7ef0b9480d48b5baae17d096234b452023-09-22T08:51:50ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2020-09-011692183219510.1080/21645515.2020.17883001788300Mechanistic insight into the induction of cellular immune responses by encapsulated and admixed archaeosome-based vaccine formulationsGerard Agbayani0Yimei Jia1Bassel Akache2Vandana Chandan3Umar Iqbal4Felicity C. Stark5Lise Deschatelets6Edmond Lam7Usha D. Hemraz8Sophie Régnier9Lakshmi Krishnan10Michael J. McCluskie11National Research Council CanadaNational Research Council CanadaNational Research Council CanadaNational Research Council CanadaNational Research Council CanadaNational Research Council CanadaNational Research Council CanadaNational Research Council CanadaNational Research Council CanadaNational Research Council CanadaNational Research Council CanadaNational Research Council CanadaArchaeosomes are liposomes formulated using total polar lipids (TPLs) or semi-synthetic glycolipids derived from archaea. Conventional archaeosomes with entrapped antigen exhibit robust adjuvant activity as demonstrated by increased antigen-specific humoral and cell-mediated responses and enhanced protective immunity in various murine infection and cancer models. However, antigen entrapment efficiency can vary greatly resulting in antigen loss during formulation and variable antigen:lipid ratios. In order to circumvent this, we recently developed an admixed archaeosome formulation composed of a single semi-synthetic archaeal lipid (SLA, sulfated lactosylarchaeol) which can induce similarly robust adjuvant activity as an encapsulated formulation. Herein, we evaluate and compare the mechanisms involved in the induction of early innate and antigen-specific responses by both admixed (Adm) and encapsulated (Enc) SLA archaeosomes. We demonstrate that both archaeosome formulations result in increased immune cell infiltration, enhanced antigen retention at injection site and increased antigen uptake by antigen-presenting cells and other immune cell types, including neutrophils and monocytes following intramuscular injection to mice using ovalbumin as a model antigen. In vitro studies demonstrate SLA in either formulation is preferentially taken up by macrophages. Although the encapsulated formulation was better able to induce antigen-specific CD8+ T cell activation by dendritic cells in vitro, both encapsulated and admixed formulations gave equivalently enhanced protection from tumor challenge when tested in vivo using a B16-OVA melanoma model. Despite some differences in the immunostimulatory profile relative to the SLA (Enc) formulation, SLA (Adm) induces strong in vivo immunogenicity and efficacy, while offering an ease of formulation.http://dx.doi.org/10.1080/21645515.2020.1788300archaeosomeadjuvantsulfated lactosyl archaeolslaarchaeolglycolipidvaccine |
| spellingShingle | Gerard Agbayani Yimei Jia Bassel Akache Vandana Chandan Umar Iqbal Felicity C. Stark Lise Deschatelets Edmond Lam Usha D. Hemraz Sophie Régnier Lakshmi Krishnan Michael J. McCluskie Mechanistic insight into the induction of cellular immune responses by encapsulated and admixed archaeosome-based vaccine formulations Human Vaccines & Immunotherapeutics archaeosome adjuvant sulfated lactosyl archaeol sla archaeol glycolipid vaccine |
| title | Mechanistic insight into the induction of cellular immune responses by encapsulated and admixed archaeosome-based vaccine formulations |
| title_full | Mechanistic insight into the induction of cellular immune responses by encapsulated and admixed archaeosome-based vaccine formulations |
| title_fullStr | Mechanistic insight into the induction of cellular immune responses by encapsulated and admixed archaeosome-based vaccine formulations |
| title_full_unstemmed | Mechanistic insight into the induction of cellular immune responses by encapsulated and admixed archaeosome-based vaccine formulations |
| title_short | Mechanistic insight into the induction of cellular immune responses by encapsulated and admixed archaeosome-based vaccine formulations |
| title_sort | mechanistic insight into the induction of cellular immune responses by encapsulated and admixed archaeosome based vaccine formulations |
| topic | archaeosome adjuvant sulfated lactosyl archaeol sla archaeol glycolipid vaccine |
| url | http://dx.doi.org/10.1080/21645515.2020.1788300 |
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